1. Field of the Invention
This invention pertains generally to nanofluidic devices, and more particularly to electronic devices for fluidic sensing and control, including functionalized nanochannels providing modifiable channel geometry and ionic environment and devices fabricated therefrom.
2. Description of Related Art
In recent years microfluidics and nanofluidics have arisen as important technologies dealing with the behavior, precise detection, control and manipulation of microliter, nanoliter and even down to femtoliter volumes of fluids. Applications for microfluidics and nanofluidics are wide ranging and of increasing interest in the fields of chemistry, engineering, biotechnology (e.g., DNA, lab-on-a-chip), and so forth. Advances in microfluidics are revolutionizing molecular biology procedures for enzymatic analysis (e.g., glucose and lactate assays), DNA analysis (e.g., polymerase chain reaction and high-throughput sequencing), and proteomics. One of the important aspects of microfluidic biochip design is integrating assay operations such as detection, as well as sample pre-treatment and sample preparation on one chip.
Continued developments are arising in the area of DNA research with using microfluidics. Early biochips were largely based on the concept of a DNA microarray (e.g., the GeneChip DNAarray from Affymetrix) which is a piece of glass, plastic or silicon substrate on which pieces of DNA (probes) are affixed in a microscopic array. Protein arrays have been similarly configured with different capture agents used to determine the presence and/or amount of proteins contained in biological samples.
Increasingly, interest is being directed toward the nanofluidic realm. Nanofluidics is generally considered the study of the behavior, manipulation, and control of fluids that are confined to structures of nanometer (typically 1-100 nm) characteristic dimensions (1 nm=10−9 m). The design of these structures often diverges from the microfluidic realm in that fluids confined in these structures exhibit physical behaviors not observed in larger structures as a consequence of the characteristic changes which arise as the physical scaling lengths of the fluid, (e.g., hydrodynamic radius and Debye length) begin to converge on the nanostructural dimensions.
A number of shortcomings exist with existing fluidic devices. Some of the drawbacks with existing devices relate to the transient nature of the testing (non-continuous) as well as the difficulty in registering results.
Accordingly, a need exists for nanofluidic device technology which can be run continuously while readily registering results. The nanofluidic devices according to the present invention fulfill those needs and others, while overcoming drawbacks of previous devices.
The detection and analysis of interactions between biological molecules is a significant area of research in the healthcare and biotechnology fields. Many molecular detection, analysis and separation techniques have been developed and validated in recent years. For most processes, efficiency is a result of a trade-off between sensitivity, specificity, ease of operation, cost, speed and avoidance of false positives. Typical biological sensing techniques require a series of preparation steps, a number of reagents and schemes to separate components, a relatively large sample size and complex data analysis.
Miniaturization and mechanization of biological sensing techniques can lower sample sizes, reduce the time and expense of the process and increase diagnostic sensitivity. Emerging micro- and nano-technologies can decrease the size, weight and cost of sensors and sensor arrays by orders of magnitude, and increase their spatial and temporal resolution and accuracy. Novel functional materials such as quantum dots, photonic crystals, nanowires, carbon nanotubes, porous membranes, porous silicon and sol-gel matrices incorporating biomolecules have been used as sensing elements with various possible detection mechanisms.
Hollow inorganic nanotubes are of particular interest due to their potential applications in bioanalysis and catalysis. For example, silica nanotubes are of special interest because of their hydrophilic nature, easy colloidal suspension formation, and surface functionalization accessibility for both inner and outer walls. Such modified silica nanotubes and nanotube membrane have shown potential applications for bioseparation and biocatalysis.
In addition, one-dimensional nanostructures (nanotubes and nanowires) have also made miniaturized chemical and biological sensing elements possible. The ultrahigh surface to volume ratios of these structures make their electrical properties extremely sensitive to surface-adsorbed species, as has been shown with carbon nanotubes, functionalized silicon nanowires and metal nanowires.
Chemical and biological nanosensors are advantageous because of their potential for detecting very low concentrations of biomolecules or pollutants on platforms small enough to be used in vivo or on a microchip. For example, a room temperature photochemical NO2 sensor has been demonstrated based on individual single-crystalline oxide nanowires and nanoribbons.
Chemical/sensing systems have also been developed using silica tubular membranes creating a new class of molecular sieves for molecular separation and electrochemical sensing based on the size of the molecules as well as interaction of the molecules with the surface functional groups of the tube. Normally, an inorganic nanotube membrane (polycarbonate or porous alumina) is set up to separate two salt solutions and a constant transmembrane potential is applied, then the transmembrane current is measured. When an analyte of comparable dimensions to the tube diameter is added to one of the solutions, a decrease in transmembrane current is sensed because of the current blocking by the molecules. Using such schemes, very small traces of different ions and molecules can be detected. These experiments, however, have all relied on using entire membranes as sensing elements. No significant efforts have been placed on single tube sensing, although the use of single nanotube sensing would obviously represent the miniaturization limit.
Nanofluidic channels and nanopores having dimensions comparable to the size of biological macromolecules such as proteins and DNA are important in applications such as single molecule detection, analysis, separation, and control of biomolecules. Previous work on nanopore or nanotube based single molecule detection can be broadly classified into two categories, namely: (i) non-functionalized nanopores; (ii) functionalized nanopores. Almost all of the prior work has involved the transmembrane protein ion channel α-Hemolysin (α HL) embedded in a suspended membrane separating two chambers filled with ionic solution. The entrance on the top (cis) side is about 2.6 nm in diameter whereas the narrow channel through the membrane that is closer to the bottom end (trans) is 1.4 nm in diameter. When a voltage bias of 120 mV is applied across the ion channel, an ionic current of about 120 pA is produced for ionic concentrations of 1 MKCI (the resistance is approximately 109Ω). However, biological nanopores such as α-hemolysin offer single molecule sensitivity but are labile and difficult to handle.
However, inorganic channels on solid state chips have advantages over organic channels including providing better control over channel geometry, increased mechanical, electrical, thermal and chemical stability and are more amenable to integration into functional systems.
Therefore, a need exists for nanofluidic devices and nanotube structures which can be readily implemented, such as within fluidic sensing applications. The present invention fulfills those needs and others, while overcoming the drawbacks inherent in prior nanodevice and nanostructure approaches.